We will continue to evaluate the mechanisms of cell-mediated inhibition of tumor growth in vivo. During the past two years, we have shown that rat lymphoid cells stimulated in an in vitro secondary immune response to a syngeneic lymphoma become cytotoxic in vitro and show a markedly increased ability to confer passive antitumor protection. We have also shown that these highly reactive cells inhibit tumor growth in part by recruiting host effector cells. The in vitro generation of specific lytic activity was observed to be enhanced by the presence of a second specific immune reaction to BCG within the culture. These studies have provided a model which may allow (1) an analysis of the mechanism of generation of effector cells and the mechanism of tumor growth inhibition in vivo mediated by such cells; (2) the development of a potential immunotherapeutic approach to neoplastic disease; and (3) an analysis of immunoadjuvants such as BCG in the potentiation of the generation of specific antitumor responses. In the proposed studies, we wish to continue to analyze the mechanism by which lymphocytes sensitized in vitro prevent tumor growth in vivo; and to evaluate the immunotherapeutic potential of such cells for transplanted and primary tumors. The extent to which prevention of tumor growth involves participation of host cells, e.g., macrophages, recruited by transferred activated lymphoid cells will be assessed. The presence of cellular or humoral factors present in tumor-bearing animals which potentially can interfere with the activity of these cells will be determined. We will also study the antigens associated with the generation or expression of antitumor activity and the role of immunoadjuvants such as BCG on the generation of specific antitumor responses. These studies should lead to a better understanding of host cellular immune mechanisms which mediate rejection of neoplastic cells; they may provide a rational basis for the passive cellular immunotherapy of tumors.